Abstract
The aimof the present work was to study the pharmacological activity of a low-molecular arginase II selective inhibitor (low-molecular compound with laboratory code ZB49) with the chemical formula 2-{1-[3-(3-[chloroisoxazole-5-yl) propyl] piperidin-4-yl}-6-(digibroxyboryl) norleucine dihydrochloride) using a model of monocrotaline-induced pulmonary hypertensionMaterials and methods.The work was performed on 40 adult male Wistar rats weighing 180– 220 g. The simulation of monocrotaline pulmonary hypertension was performed on 20 animals using a subcutaneous injection of an alcohol-aqueous solution of monocrotaline (MCT) at a dose of 60 mg/kg in a volume of 0.5 ml per animal. 7 days after the MCT injection, the administration of the studied pharmaceutical substance (PS) (laboratory code ZB49) was started at a dose of 5 mg/kg. ZB49 was administered intragastrically, once a day with the administration duration of 21 days.Results.Under the intragastric FS ZB49 administration at a dose of 5 mg/kg, a statistically significant decrease in the coefficient of endothelial dysfunction, systolic right ventricle pressure (SRVP), average the right ventricle pressure (ARVP), diastolic right ventricle pressure (DRVP), maximum contraction rate (dP/dt max) and minimum contraction rate (dP/dt min) was established at the background of the simulation of monocrotaline-induced pulmonary hypertension. At the same time, a statistically significant positive effect of ZB49 on the blood gas composition was established.Conclusion.The study has confirmed the possibility of using arginase inhibitors to prevent the development of endothelial dysfunction and the disorders of nitric oxide metabolism in pulmonary arterial hypertension. Among the substances of this group, arginase II selective inhibitors should be considered as the most promising.Conflict of interest: the authors declare no conflict of interest.
Highlights
The study has confirmed the possibility of using arginase inhibitors to prevent the development of endothelial dysfunction and the disorders of nitric oxide metabolism in pulmonary arterial hypertension
Влияние моделируемой патологии с помощью ZB49 на коэффициент эндотелиальной дисфункции при моделировании монокроталиновой легочной гипертензии и ее коррекции
ZB49 effect on the cardiac hemodynamics indicators against the background of the simulation of monocrotaline pulmonary hypertension
Summary
The study has confirmed the possibility of using arginase inhibitors to prevent the development of endothelial dysfunction and the disorders of nitric oxide metabolism in pulmonary arterial hypertension. For citation: Korokina L.V., Pokrovskii M.V., Pazhinskii L.V., Kochkarova I.S., Korokin M.V. Study of the Pharmacological Activity of Low-Molecular Arginase II Selective Inhibitor Using a Model of Monocrotaline-Induced Pulmonary Hypertension. В исследованиях установлено, что ингибирование аргиназы II способствует увеличению продукции оксида азота и предотвращению эндотелиальной дисфункции [8,9,10,11,12,13,14,15]. Патогенетически обоснованной при артериальной легочной гипертензии видится возможность использования веществ, являющихся ингибиторами аргиназ, для увеличения синтеза оксида азота и предотвращения развития эндотелиальной дисфункции.
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